Interpretive Summary: High dietary calcium (Ca) in the context of a dairy food matrix has been shown to reduce obesity development and associated inflammation in diet-induced obese (DIO) rodents. The influence of Ca and dairy on these phenotypes in the context of pre-existing obesity is not known. Furthermore, interpretations have been confounded historically by differences in body weight gain among DIO animals fed dairy-based protein or high Ca. Adiposity along with associated metabolic and inflammatory outcomes were measured in DIO mice previously fattened for 12 wk on a soy protein-based obesogenic high fat diet (45% energy, 0.5% adequate Ca), then fed one of three high fat diets (n = 30/group) for an additional 8 wk: control (same as lead-in diet), high-Ca (1.5% Ca), or high-Ca + nonfat dry milk (NFDM). Mice fed high-Ca + NFDM had modestly, but significantly, attenuated weight gain compared to mice fed high-Ca or vs. controls (P < 0.001), whereas mice fed high-Ca alone had increased weight gain compared to controls (P < 0.001). Total measured adipose depot weights between groups were similar, as were white adipose tissue inflammation and macrophage infiltration markers (e.g., TNFa, IL-6, CD68 mRNAs). Mice fed high-Ca + NFDM had significantly improved glucose tolerance following a glucose tolerance test, and markedly lower liver triglycerides compared to high-Ca and control groups. Conclusions: Improved metabolic phenotypes in pre-fattened DIO mice following provision of a diet enriched with dairy-based protein and carbohydrates appeared to be driven by non-Ca components of dairy, and were observed despite minimal differences in body weight or adiposity. Thus, dairy foods appear to contain factors independent of calcium that positively impact metabolism by reducing liver fat and improving blood sugar control. These effects in mice are not dependent on major changes in body weight, suggesting that if results can be applied to the human condition, improvement in dietary quality and dairy intake could have positive effects on health that do not require changes in body weight.

Technical Abstract: High dietary calcium (Ca) in the context of a dairy food matrix has been shown to reduce obesity development and associated inflammation in diet-induced obese (DIO) rodents. The influence of Ca and dairy on these phenotypes in the context of pre-existing obesity is not known. Furthermore, interpretations have been confounded historically by differences in body weight gain among DIO animals fed dairy-based protein or high Ca. Adiposity along with associated metabolic and inflammatory outcomes were measured in DIO mice previously fattened for 12 wk on a soy protein-based obesogenic high fat diet (45% energy, 0.5% adequate Ca), then fed one of three high fat diets (n = 30/group) for an additional 8 wk: control (same as lead-in diet), high-Ca (1.5% Ca), or high-Ca + nonfat dry milk (NFDM). Mice fed high-Ca + NFDM had modestly, but significantly, attenuated weight gain compared to mice fed high-Ca or vs. controls (P < 0.001), whereas mice fed high-Ca alone had increased weight gain compared to controls (P < 0.001). Total measured adipose depot weights between groups were similar, as were white adipose tissue inflammation and macrophage infiltration markers (e.g., TNFa, IL-6, CD68 mRNAs). Mice fed high-Ca + NFDM had significantly improved glucose tolerance following a glucose tolerance test, and markedly lower liver triglycerides compared to high-Ca and control groups. Conclusions: Improved metabolic phenotypes in pre-fattened DIO mice following provision of a diet enriched with dairy-based protein and carbohydrates appeared to be driven by non-Ca components of dairy, and were observed despite minimal differences in body weight or adiposity.